The invention relates to the field of molecular biology and microbiology. More particularly, the invention relates to monacolin K biosynthesis genes.
Monascus has been applied in the food industry for thousands of years in China. Recently, it was discovered that Monascus produces several bioactive substances. These bioactive substances are mainly the secondary metabolites of Monascus, including substances for reducing hypertension, substances of anti-putrefaction bacteria such as monascidin, anti-cancer substances, substances for lowering blood sugar, ergosteral, anti-oxidants, and inhibitors of cholesterol synthesis such as monacolin. Therefore, Monascus has been valued as a functional health food in recent years.
Monacolin K, the cholesterol-synthesis inhibitor produced by Monascus, was first isolated from the medium of Monascus rubber by SANKYO CO., LTD. Merck & Co., Inc. then found the same substance from the medium of Aspergillus terreus denominated as lovastatin and acted as a HMG-COA reductase inhibitor. Monacolin K belongs to polyketides and the structure thereof shares similarity with HMG-CoA. Therefore, Monacolin K competitively inhibits cholesterol synthesis with HMG-CoA, and HMG-CoA reductase cannot catalyze HMG-CoA to form mevolonate, resulting in reduction of cholesterol synthesis.
The secondary metabolites of polyketides produced by fungi express structural variety and unique characteristics which do not exist in other bacteria (O'Hagan, 1995). These characteristics are also expressed in enzyme variety of polyketide synthesis. Monacolin K produced by Monascus is a member of the polyketide group, and it is found that the various polyketides are produced by condensation of acetyl CoA catalyzed by polyketide synthase (PKS) (Kennedy et al., 1999; and Abe et al., 2002). From the study of polyketide synthase combined with combinatorial biosynthesis, the development of novel polyketides has great potential (Mc Daniel et al., 1999), and the novel polyketides will be another new rout for screening effective medications.